Clinical Trial: FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Study of Intravenously Administered FAU (1-(2'-Deoxy-2'-Fluoro-B-D-arabinofuranosyl) Uracil, NSC#678515) in Patients With Advanced Solid Tumors

Brief Summary: Drugs used in chemotherapy, such as FAU, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. This phase I trial is studying the side effects and best dose of FAU in treating patients with advanced solid tumors or lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of FAU in patients with advanced solid tumors or lymphoma.

II. To determine the dose-limiting toxicity and maximum tolerated dose (MTD) of FAU in these patients.

SECONDARY OBJECTIVES:

I. To observe the clinical response in patients treated with FAU. II. To characterize the pharmacokinetics of FAU in these patients. III. To explore whether an association exists between pre-treatment 18F-FAU PET standardized uptake value levels and time to tumor progression after treatment with unlabeled FAU.

IV. To estimate the protein levels of thymidylate synthase (TS) in archival tumor tissue samples and to compare them with thymidine kinase (TK) and TS protein levels and TK and TS mRNA levels in fresh tumor tissue samples from patients treated at the MTD.

V. To explore the relationship between genetic polymorphisms of TS and tumor 18F-FAU uptake.

OUTLINE: This is a multicenter study.

Patients receive FAU IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed for 30 days.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Maximum tolerated dose, defined as the dose at which no more than 1/6 patients develops dose-limiting toxicity, graded by NCI CTCAE version 4.0 [ Time Frame: Up to 28 days ]

Original Primary Outcome:

  • Dose-limiting toxicity of FAU as assessed by NCI CTCAE version 3.0
  • Maximum tolerated dose of FAU


Current Secondary Outcome:

  • Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [ Time Frame: Up to 30 days ]
    Response will be described by point estimates and exact confidence intervals.
  • Pharmacokinetics of FAU, including Cmax, Tmax, AUC 0-last, AUC 0-infinity, CL, t1/2, and Vss [ Time Frame: Days 1 and 22 of course 1 at pre-treatment; at the end of infusion; and following the end of infusion at 15 and 30 minutes and 1, 2, 4, 8, and 24 hours ]
    All pharmacokinetic parameters will be summarized with standard descriptive statistics.


Original Secondary Outcome:

  • Response
  • Pharmacokinetics of FAU
  • Relationship between pre- and post-treatment 18F-FAU PET standardized uptake value levels and time to tumor progression
  • Comparison of protein levels of thymidylate synthase (TS) in archival tumor tissue samples with thymidine kinase (TK) and TS protein levels and TK and TS mRNA levels in fresh tumor tissue samples
  • Relationship between genetic polymorphisms of TS and tumor 18F-FAU uptake


Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 8, 2008
Date Started: July 2009
Date Completion:
Last Updated: January 6, 2014
Last Verified: January 2014